A Morinda Officinalis Extracellular Vesicles-Encapsulated Redox Homeostasis Modulatory Hydrogel Promotes Growth Plate Injury Repair by Regulating the Oxidative Stress Microenvironment

It is now understood that oxidative stress, characterized by an excess of reactive oxygen species (ROS) within growth plate injury sites, can impede cartilage repair through various mechanisms. Morinda officinalis (MO), a traditional Chinese herbal medicine, possesses potent antioxidant properties. Furthermore, extracellular vesicles (EVs) derived from plants exhibit comparable physical and chemical characteristics to their parent plants, along with favorable tissue permeability and biocompatibility. Herein, it develops a ROS-sensitive hydrogel by self-crosslinking two natural extracellular matrix (ECM)-derived components: polyvinyl alcohol (PVA) and chondroitin sulfate grafted with phenylboric acid (CSBA). The hydrogel is subsequently combined with MO-derived EVs (MO-EVs) to eliminate excess ROS from the damaged microenvironment and release MO-EVs as needed to facilitate growth plate damage healing. In vitro studies revealed that a CSBA-PVA hydrogel containing MO-EVs facilitated the restoration of chondrocyte mitochondrial function by activating the NRF2-HO-1/NQO1 pathway, thereby enhancing endogenous antioxidant capacity. Furthermore, in vivo results reveal that implantation of CSBA-PVA hydrogel loaded with MO-EVs significantly inhibited bone bridge development and facilitated cartilage restoration within the growth plate. CSBA-PVA@MO-EVs therapy brings huge prospects as a therapeutic approach, offering novel insights and therapeutic strategies for treating growth plate injuries.